1. Prostaglandin E2 significantly inhibits the renin reaction in whole plasma as well as in the isolated system of semi-purified human renin and human renin substrate. The inhibitory effect of prostaglandin A2 was less marked in whole plasma and absent in the isolated system.
2. The inhibitory effect of prostaglandin E2 was more marked in normal than hypertensive plasma and was maximal at the lowest concentration used. In hypertensive plasma the maximal inhibitory effect was achieved at tenfold higher concentrations.
3. In normal plasma prostaglandin E2 does not affect the rate of product formation (k5 = k6), but inhibits the overall renin reaction by decreasing the total amount of available enzyme-substrate and enzyme-substrate modifier complex (K2K3).
4. In hypertensive plasma prostaglandin E2 acts as a potential accelerator of the rate of product formation (k6k5). In the range of substrate concentration employed, the apparent inhibitory effect is explained by an even greater lack of available complex (K2K3). This behaviour in hypertensive plasma is consistent with the presence of an additional modifier (? activator).