Serotonin 5-HT(1A) receptors were characterized in rat resting lymphocytes obtained by cardiac puncture with the use of the ligand [3H]8-hydroxy-2-(di-n-propylamino)tetralin. Selectivity of the specific binding was demonstrated by inhibition experiments with various serotonergic and nonserotonergic drugs. The rank order of potency for inhibition was WAY-100478>pindobind>NAN-190>buspirone>imipramine>serotonin. While pimozide, desipramine, nomifensine, haloperidol and sulpiride did not inhibit the binding. Kinetic parameters calculated from saturation experiments indicated one site of interaction, with an equilibrium dissociation constant of 2.50 nM and maximum binding capacity of 487.21 nmol/10(6) cells. Complete dissociation was obtained with serotonin as the displacement agent, and equilibrium dissociation constant calculated by association and dissociation experiments was 2.03 nM. Thus, serotonin 5-HT(1A) receptors are present in resting lymphocytes. The in vivo administration of the mitogens lipopolysacharide (0.1 mg/kg, 18 h) or concanavalin A (0.2 mg/kg, 18 h) increased the number of sites. The elevation produced by the latter was of higher magnitude than that of lipopolysacharide, and two sites of the binding were determined by isotopic dilution. Immobilization stress (1 h daily for 7 days) also resulted in a significant increase of binding capacity, but was smaller than that produced by the mitogens. The affinity of binding was not affect by the treatments. The results indicate that serotonin 5-HT(1A) receptors are modulated by unspecific and specific immune system activation, as well as by a potent stress condition, which might result in relevant functional modifications in the response of rat lymphocytes.