Benzene and toluene, commonly used solvents, possess neurotoxic and immunotoxic effects. Male CD-1 mice were continuously fed drinking water containing 0, 31, 166 and 790 mg/l benzene and 0, 17, 80 and 405 mg/l toluene, respectively. The concentrations of hypothalamic norepinephrine (NE) and its metabolite vanillylmandelic acid (VMA), circulating corticosterone and adrenocorticotropic hormone (ACTH), and lymphocyte-derived interleukin-2 (IL-2) activity were evaluated after 28 days of exposure to each solvent. Serum corticosterone was also measured at pretreatment, 2, 7, and 14 days of exposure. The concentrations of NE, VMA, ACTH and corticosterone were increased following exposure to these solvents. Benzene increased corticosterone levels in mice after 7 days (166 and 790 mg/l) and at 28 days (790 mg/l). Toluene elevated corticosterone levels at 14 and 28 days at the 405 mg/l exposure. IL-2 production by mouse T-lymphocytes was suppressed in the two higher benzene-treated groups, while toluene decreased IL-2 synthesis at the highest level only. Both benzene and toluene exposures stimulated hypothalamic-pituitary-adrenocortical (HPA) activity. Elevated corticosterone has been reported to inhibit IL-2 production and impair immunocompetence. Organic solvents may have, at least partially, an additive adverse effect on immune function via activated HPA status.