Animal and human studies have related the sleeping/waking brain to the immune system. Because women are more susceptible to certain immunological illnesses, and sex steroids regulate immune functions, it was investigated whether the diurnal sleep/wake pattern of aspects of cellular immune functions and interleukin-1 (IL-1) and IL-2-like activities differed during low and high progesterone phases of the menstrual cycle. Eleven healthy women, mean age 24 y, were assessed over 24 h with serial venous blood samples. Peripheral blood monocytes were assayed for mitogen responses, i.e. phytohemagglutin (PHA) and pokeweed (PWM) and natural killer (NK) cell activities. Plasma was assayed for IL-1 and IL-2-like activities, cortisol and progesterone. Data were standardized by Z transformation and analysed by repeated-measures analysis of variance by comparing high (N = 5) vs. low (N = 6) progesterone phases. During the high progesterone phase, delayed slow-wave sleep (SWS) onset time and reduced amount of SWS was accompanied by a delay in the decline of NK cell activity, but rise in PHA activity following sleep onset. With the low progesterone phase, the pattern was similar to men with an early sleep decline in NK cell and late sleep rise in PHA activities. PWM rose during the night and plasma IL-1-like activity peaked during midday and during nocturnal sleep irrespective of the amount of progesterone. Slow-wave sleep and sleep-related NK cell and PHA activities differed over the menstrual cycle, but not PWM response. Increases in plasma IL-1 functions during midday and night are consistent with predisposition to sleepiness during these times.