We performed studies using an animal model of thermal injury to confirm the observed decrease in interleukin 2 (IL-2) production in burned patients and to explore the underlying mechanisms. Ten mice subjected to a 25% scald were compared with ten anesthetized littermates (controls) and six untreated mice (normal mice) 1, 3, 5, 7, 10, 14, and 21 days after burn. Production of IL-2 by splenocytes was stimulated by concanavalin A alone, or in the presence of the cyclooxygenase inhibitor indomethacin or flurbiprofen. The IL-2 content of the resulting supernatant was determined by the response of the IL-2-dependent cell line CTLL-2. The IL-2 production was significantly suppressed in the burned mice at three days (mean +/- SEM, 30.9% +/- 5.2%), five days (19% +/- 5.5%), seven days (41.6% +/- 6.4%), and 21 days (20% +/- 4.5%). Significant enhancement of IL-2 production by indomethacin was seen in the burned group (mean, 95%), but not in controls (mean, 23.8%) or normal mice (mean, 17.2%), and similar effects were seen with flurbiprofen. In separate experiments the effects of exogenous prostaglandin E2 on lymphocyte blastogenesis and IL-2 production were studied, and an increased susceptibility to the inhibitory effects of prostaglandin E2 was observed following thermal injury.