Rats 4 to 7 days after weaning received intraperitoneal (i.p.) injections of vehicle (baseline day), and either serum (2 mL of lyophilized rabbit serum), 140 mg of rat albumin, or hyperosmotic NaCl (experimental day). Injections were given 1 h before light onset. Sleep-wake activity and cortical brain temperature were recorded during the subsequent 12-h light period. The intensity of non-rapid eye movement sleep (NREMS) was characterized by the power density values of the electroencephalogram slow-wave activity. The sera and albumin preparations enhanced both NREMS and slow-wave activity for 5 to 6 h starting during Hour 2 after light onset. Rapid eye movement sleep (REMS) tended to decrease. Modest (0.6 degrees C maximum deviation) biphasic changes were observed in cortical brain temperature with initial decreases for 3 h followed by rises between Hours 3 and 9 of the light period. There were no differences in the sleep responses to albumin between male and female rats. Albumin also enhanced NREMS in young rats on a protein-rich diet. A significant negative correlation was found between the NREMS promoting activity of albumin injections and the body weight of the rats. NaCl solution with the same osmolarity as that of the albumin solution failed to alter sleep. I.p. albumin injection elicited significant increases in the concentrations of cholecystokinin-like immunoreactivity in the plasma. Sleep-promoting materials (hormones) in the albumin fraction, the calorigenic or nutritional value of proteins, the release of somnogenic cytokines by albumin, or endogenous humoral mechanisms stimulated by proteins (e.g., cholecystokinin or the somatotropic axis) might mediate the enhanced sleep after albumin.