The influence of 4 murine monoclonal antibodies (MAbs) directed against surface determinants of a metastasizing rat adenocarcinoma (BSp73ASML) on metastatic spread was evaluated and compared to their in vivo binding as well as to the induction of a humoral anti-MAb response, especially with respect to the development of anti-idiotypic (ID) antibodies of the internal image type. In a protocol of explicit immunization, all 4 MAbs transiently inhibited metastatic growth. Survival was prolonged only with one MAb (4.4ASML). With another MAb (1.1ASML), directed against a new variant form of CD44, metastatic growth was accelerated after transient retardation. Retardation of metastatic growth correlated with the humoral anti-MAb response. This accounted for the isotype- as well as for the idiotype-specific response. An exception was noted after immunization with MAb 1.1ASML. Rats with high levels of anti-1.1ASML antibodies, which inhibited binding to the tumor cells (internal image-type antibodies) showed accelerated metastatic spread. Data are interpreted to mean that MAb-induced inhibition of metastatic spread may be based on 2 independent mechanisms: blockade of metastasis-associated epitopes (i. e., with MAb 1.1ASML) and induction of an anti-mouse lg response. In the latter case it was irrelevant whether the response was isotype- or idiotype-specific.