Fully occupied with work, both physical and mental in due proportion, for more than ten hours every secular day, when evening comes he finds himself unable to read long on account of a drowsiness supposed to be of a purely physiological character. With a full breakfast at about 7:30, a full dinner at about 2:30, and a light evening meal about 7, and no stimulants, or tea, or coffee at any time, he finds, as a matter of not invariable but general habit, that by half past 8 drowsiness becomes so dominant that it becomes almost impossible, and generally impracticable, to avoid falling asleep in his chair while attempting to read, even though ordinary conversation be carried on around him. The first trial to combat or prevent this drowsiness was made with caffeine. The first specimen used was a very beautiful article made by Merck of Darmstadt, and after that by pure specimens made for the purpose, the two kinds being found identical in effect. Commencing with a one grain dose at about 6:30 P.M., on alternate evenings, leaving the intermediate evenings in order to be sure that the nightly tendency still persisted, and increasing by half a grain each alternate evening, no very definite effect was perceived, until the dose reached 2½ grains, and this dose simply rendered the tendency to sleep resistible by effort. After an interval of three evenings, with the tendency to sleep recurring with somewhat varying force each evening, a dose of 3 grains was taken, the maximum single dose of the German Pharmacopoeia. This gave a comfortable evening of restedness, without sleep or any very strong tendency to it until ten o'clock. Without anything to counteract sleep, the rule was to read with difficulty by nine, without much comprehension by quarter past nine, and either be asleep or go to bed by half past nine. The 3 grain dose of caffeine repeatedly obviated all this discomfort up to ten o'clock, but did not prevent the habitual, prompt, and sound sleep, from the time of going to bed till morning. This was the model established, upon and by which to measure all the other agents, and they were never taken nearer than on alternate evenings, with occasional longer intervals, especially when the final doses of record were to be taken. The next agent tried in precisely this same way was coca; and knowing that the quality of that which was attainable was very low, the commencing dose of the leaf in substance was 2 drachms, or about 8 grammes. This gave no very definite effect, but 2½ drachms did give a definite effect, and a subsequent dose of 2½ fluid drachms of a well made fluid extract of coca gave about the same effect as 2½ grains of caffeine. Three fluid drachms of the fluid extract were about equivalent to 3 grains of caffeine. Both the coca used and the fluid extract were then assayed by the modern methods, for the proportion of the alkaloid they contained.