Infectious disease is known to alter both sleep patterns and hydrocortisone (cortisol) concentrations in rabbits. Moreover, the sleep-altering effects of microbial infections are likely to be mediated via endogenous immune modulators whose actions are attenuated by glucocorticoids. To evaluate the relationships between sleep and glucocorticoids during infectious disease, the effects of cortisone administration (20 mg/kg, im) on sleep were examined before and after inoculation of rabbits with Staphylococcus aureus or Escherichia coli. When administered alone, cortisone did not alter the amount of time spent in slow-wave sleep (SWS) but did reduce electroencephalographic (EEG) slow-wave amplitudes during SWS, the number of bouts of SWS and the amount of time spent in rapid-eye-movement sleep. The duration of individual bouts of SWS was increased after cortisone treatment. Bacterially infected rabbits developed biphasic changes in sleep patterns that were characterized by an initial increase and a subsequent decrease both in SWS time and in EEG slow-wave amplitudes during sleep. Cortisone treatment attenuated these effects in S. aureus-inoculated rabbits. In contrast, cortisone treatment did not alter the initial phase of enhanced sleep in E. coli-inoculated rabbits but did attenuate the subsequent sleep suppression. These data indicate that glucocorticoid administration is associated with an attenuated sleep response in bacterially inoculated rabbits.