Repeated determinations of the elevated serum acid phosphatase activities in five patients with advanced prostatic cancer were found to be highly variable during 24 to 48 hours of observation. Samples collected every three hours had fluctuations of 44% to 97% around the 24- to 48-hour mean values. These fluctuations appeared to be random, had no apparent circadian rhythm, and were unrelated to concurrent medications or activity. These spontaneous variations indicate the need for caution when using serial serum acid phosphatase determinations as an indicator of the response of prostate cancer to therapy. Elevated serum alkaline phosphatase activities did not show these extreme fluctuations.