Apparent generation.of angiotensin I (AI) in human plasma depends on choice of angiotensinase and converting enzyme inhibitors, pH of incubation, and unknown factors in individual plasma samples. The shape of pH curves for AI generation in human plasma varies with choice of enzyme inhibitors, suggesting that such curves reflect a titration of inhibitor effectiveness as well as a measure of renin activity. AI is generated from anephric plasma incubated at acid but not at neutral pH, suggesting the participation of acid proteases. Lowering the pH of incubation of patient samples from 7.4 to 5.5 does not cause an invariable increase in AI generation. The effects of acidifying plasma on AI production vary greatly from sample to sample, and this variabiltiy should be taken into account when measurements of plasma renin acitvity are carried out under unphysiologic conditions. © 1974 by The Endocrine Society.