Diurnal changes in the basal levels of plasma cortisol were studied in the female guinea pig. Plasma cortisol levels were determined at 8 bleeding times during the entrained 24 h photoperiod (14 h light/10 h dark: lights on 06.00 h). Plasma cortisol levels remained low during the dark phase of the cycle ranging between 6.4 and 9.0 microgram/100 ml. However, at 4 h prior to the onset of the light phase of the photoperiod, a dramatic rise in the plasma cortisol level was measured, which peaked between 04.00 and 08.00 h at 12.3 microgram/100 ml. A subsequent decline in plasma cortisol levels was measured throughout the light phase of the cycle, reaching basal levels before the onset of the dark phase. These data indicate that a diurnal fluctuation in plasma cortisol occurs in the guinea pig which is very reminiscent of that seen in the human and in contrast with that observed in the rat.