1. Mice, whose drinking water contained sulphasalazine, sulphapyridine or 5-amino-salicylic acid, received an antigenic challenge by cholera toxin administered either orally or systemically. 2. Sulphasalazine treated mice made less specific antibody of IgA class provided the antigen also was administered orally (P = 0.009 for days 7-28). When the antigen was administered systemically, there was a vigorous anti-cholera toxin antibody response of IgG class, and a lesser IgM but only a weak IgA response. The effect of sulphasalazine in this case was confined to the IgG response, which was significantly suppressed on day 28 (P = 0.008). 3. Sulphapyridine and 5-amino salicylic acid had no significant effect on the anti-cholera toxin (CT) responses of all three classes. 4. It therefore appears that in this model, only sulphasalazine is capable of influencing the humoral immune system, the antibody class affected depending on the route of entry of antigen. This may have implications for conditions such as rheumatoid arthritis and chronic inflammatory bowel disease, for which sulphasalazine has been found useful.