Studies under controlled conditions of lighting and temperature revealed clear evidence of circadian periodicity with respect to the number of PFC present in the spleens of BALB/c mice 3 or 4 days after immunization with SRBC. Striking differences in proliferative responses of spleen lymphocytes to PHA or Con A were also observed at two different circadian times. Large proliferative responses occurred at the time when injection of antigen and/or sampling for PFC yielded a low PFC formation (early in the daily dark span) and small proliferative responses occurred at the time when antigen injection and sampling yielded high formation of PFC (early in the daily light span). These findings indicate that care should be taken to control the circadian timing of stimulation and sampling in studies of immune responses, and that rhythmically varying aspects constitute a new dimension of immunologic processes awaiting further analysis in both the circadian and weekly spectral regions.

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