The object of the present investigations was delineation of the exclusive effects of cyclophosphamide (Cytoxan) on host humoral response to tumor, as evaluated by the level of circulating antigen/antibody complexes (AACs), which may reflect the chemo-responsiveness of hosts and provide a rationale for new therapeutic strategies. Our data, recorded in Copenhagen X Fischer rats bearing Dunning's R-3327 Mat Ly-Lu adenocarcinoma of the prostate, show no modulatory effect of cyclophosphamide at 10 mg/kg, a nonspecific immunosuppressive effect at 30 mg/kg, and a definite immunostimulatory effect on host humoral immunity at 100 mg/kg. Sequential determination of AAC levels at different stages of tumor growth, i.e. from the primary to the metastatic stage, performed with the original purpose of demonstrating that any disturbance in the immunoregulatory mechanism of the host was due to cyclophosphamide rather than to changes in tumor load, revealed that levels of AACs parallel disease progression in the initial stages of primary tumor growth but rapidly decrease to near-normal levels in the presence of heavy tumor burden.