1. The mechanism of increased renin activity after human plasma had been kept at −5°C for 4 days (cryoactivation) was investigated.
2. The increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0·88, P < 0·001, n = 10).
3. An inhibitor of thiol enzyme, N-ethylmaleimide did not inhibit cryoactivation.
4. Soyabean trypsin inhibitor and di-isopropylfluorophosphate (DFP) inhibited cryoactivation, suggesting that the cryoactivation may be due to the action of a trypsin-like serine enzyme.
5. In an experiment in the rat haemorrhagic shock caused parallel increments of renin activity in non-cryoactivated and cryoactivated plasma, the renin activity being about two times higher in the latter. No significant differences were found in the concentrations of renin and renin substrate between the non-cryoactivated and cryoactivated plasma samples.
6. The results may indicate that a destruction of an inhibitor of the renin—renin substrate reaction is responsible for the increase of renin activity after exposure of rat plasma to low temperature. A trypsin-like enzyme in plasma might have destroyed the inhibitor during this procedure.