Investigations in our laboratories have indicated that when Salmonella enteritidis (SE)-immune lymphokines--supernatants from concanavalin-A-stimulated T cells derived from SE-immune adult chickens--were administered intraperitoneally to 1-day-old chicks before SE challenge, they conferred protection against SE organ invasion within 24 hr. This resistance mediated by SE-immune lymphokines was associated with a concomitant increase in peripheral blood polymorphonuclear leukocytes that peaked 4 hr after SE challenge. In the present study, we evaluated efficacy of SE-immune lymphokines in protecting chicks against SE organ invasion and alterations in peripheral blood polymorphonuclear leukocyte counts. Administration of SE-immune lymphokines to chicks either 30 min or 6 days before SE challenge caused a significant reduction in SE organ invasion. However, when SE-immune lymphokines were administered 2 days after SE challenge, there was no reduction in SE organ invasion. Both prophylactic (before SE challenge) and therapeutic (after SE challenge) administration of SE-immune lymphokines caused a significant increase in numbers of peripheral blood polymorphonuclear leukocytes. Results from these studies suggest that SE-immune lymphokines have potential value as an effective prophylactic but not as a therapeutic modulator of early resistance to SE organ invasion in neonatal leghorn chicks.