The antibiotic oxytetracycline (oxyTC) was administered either by mixing with food or by intraperitoneal injections. In oxyTC treated animals decreased serum immunoglobulin levels were found. The primary anti-sheep red blood cell (SRBC) response was measured by enumerating plaque forming cells (PFC). It was observed that the PFC response was depressed by 80–95% in oxyTC treated animals. When an anti-SRBC serum was injected together with SRBC the immunosuppressive effect of oxyTC was absent. A secondary anti-SRBC response was not inhibited by oxyTC. On base of the results a model for antigen presentation and the interaction between macrophages, T- and B-like cells during primary and secondary responses in fish is proposed. In primary responses cellular interaction is needed to develop a proper immune response whereas after a high antigen dose challenge SRBC might behave as a T-independent antigen.