The effects of varying amounts (100.0-0.01 units/ml) of human interferon (IFN) alpha upon in vitro canine immune responses were studied. Exogenous heterologous species IFN-alpha suppressed B-cell differentiation in a dose-dependent fashion and enhanced interleukin-2 production (P less than 0.05) by activated T-lymphocytes. Interferon enhanced natural killer (NK) cytotoxicity when tested against NK-resistant target cells (less than 0.05). One hundred units IFN/ml increased interleukin-1 production by canine monocytes, but this effect was not statistically significant. Exogenous IFN had no discernible effect upon lectin-induced lymphocyte blastogenesis. The results of this study demonstrate that human IFN-alpha does affect various canine lymphocyte functions and these effects depend upon the in vitro assay system employed.