In the above cases rapid clotting was manifest directly after minute doses. Larger doses, however, may produce primarily not faster clotting but slower, and that may be followed in turn by a much shorter coagulation time. The figures below present such an instance: Nov. 25. 2.36--3 minutes .40--3 “ .43 Adrenin, 0.5 cubic centimeter, 1:10,000. .44--4 minutes .49--3.5 “ .53--1.5 “ .55--1.5 “ .58--2 “ 3.00--2.5 “ .03--1.5 “ .05--1.5 “ .07--2.5 “ .10--1.5 “ .14--1.5 “ .16--2.5 “ .19--3 “ .23--3 “ .30--3 “ This unexpected primary increase of coagulation time, lasting at least six minutes, is in striking contrast to the later remarkable shortening of the process from 3 to an average of 1.7 minutes for more than 20 minutes (see Fig. 27, A). [Illustration: Figure 27.--A, Primary lengthening followed by shortening of the coagulation time when adrenin, 0.5 cubic centimeter 1:10,000 (0.05 milligram), was injected slowly at 2:43. B, Lengthening of the coagulation time without shortening when the same dose was injected rapidly at 10:08.] If a strong solution, i. e., 1:10,000, is injected rapidly, the process may be prolonged as above, but not followed as above by shortening, thus: Nov. 28. 9.59--3 minutes 10.03--3 “ .08 Adrenin, 0.5 cubic centimeter, 1:10,000. .10--3 minutes .14--3.5 “ .18--3.5 “ .22--3.5 “ .26--3 “ .29--3 “ .33--3 “ There was in this case no decrease in coagulation time at any test for a half-hour after the injection, but instead a lengthening (see Fig. 27, B). Howell[102] has reported the interesting observation that repeated massive doses of adrenin given to dogs may so greatly retard coagulation that the animals may be said to be hemophilic. These two instances show that on coagulation large doses have the contrary effect to small, just as Hoskins[103] showed was true for intestinal and Lyman and I[104] showed was true for arterial smooth muscle.