"Winter kill" syndrome is a disease in channel catfish, Ictalurus punctatus, which occurs during the winter months. The syndrome, characterized by cutaneous fungal lesions, has recently been described in detail and is an infectious disease better termed "winter saprolegniosis." A ubiquitous fungus, Saprolegnia sp., is the causative organism responsible for the outbreak of disease in channel catfish rendered immunocompromised by a rapid drop in water temperature. Histological examination of fungal skin lesions from pond- or laboratory-infected channel catfish revealed a complete lack of leukocytic infiltration around invading hyphae. Presumably, the lack of an inflammatory/immune response is attributable to either low temperature-mediated in vivo immunosuppression and/or fungal suppression or evasion of the fish's immune system. The present study was initiated to determine if the fungus was suppressing or evading the channel catfish immune system. The questions asked were: whether channel catfish held at an immunologically permissive temperature (24°C) can mount an immune response if inoculated with viable Saprolegnia sp., and if so, what is the nature of the response, i.e., is it natural or acquired or humoral or cell-mediated? These questions are of great importance if a vaccine is to be developed for winter saprolegniosis. In order to determine if humoral immunity was involved, channel catfish held at 24°C were given intra-peritoneal injections of Saprolegnia sp, and monitored for the production of antibodies for two months. All injected fish failed to produce detectable antibodies, suggesting that the immune response may be predominantly cellular rather than humoral. Consequently, fish held at 24°C were given intra-muscular injections of viable Saprolegnia sp. and monitored for localized cellular immune responses. During the ensuing 16 days, fish exhibited acute phase responses, i.e., localized raised hemorrhagic lesions of ≤1 cm around the injection site were observed. The response peaked on day 8 and was totally resolved by day 16. Histopathology revealed a foreign body inflammatory response with the classical appearance of giant multinucleated cells. Granulocytes initially infiltrated the site, followed later by predominantly lymphocytes. Leukocytes were also seen attached to fungal hyphae early in the response. These results indicate that Saprolegnia sp. likely neither evades nor suppresses the channel catfish immune system. It is proposed that future therapeutic and prophylactic measures to prevent the occurrence of winter saprolegniosis should focus on enhancing cellular defenses to Saprolegnia sp.