We have previously developed 3 monoclonal anti-idiotypic antibodies (Ab2) of LOU rat origin directed against the binding site of the murine monoclonal IgM LAM8, which recognizes the small-cell lung carcinoma (SCLC)-associated sialoglycoprotein antigen sGP 90-135. The aim of this study was to compare the efficiencies of these 3 Ab2, designated LY8-229, LX8-531 and LX8-632, to induce antigen-specific immunity in different animal species without prior exposure of the recipients to the nominal antigen, and thereby possibly select an Ab2 candidate for active immunotherapy against SCLC in patients. The feasibility of this approach was further evaluated by a serological analysis of patients with SCLC compared with healthy individuals, in whom the spontaneous antibody reactivities against SCLC cell lines and Ab2 were tested. LY8-229 was shown to be the most effective Ab2 in inducing antigen-specific antibodies in BALB/c mice, CBA/J/Zur mice and one NZW rabbit. Furthermore, LY8-229 was the only Ab2 against which significantly elevated idiotype-specific antibody reactivities existed in sera of patients with SCLC. These reactivities correlated positively with binding to antigen-positive tumor cells. Our findings suggest that LY8-229 represents in its reactivity pattern the nominal SCLC antigen in humans also, and therefore may be of diagnostic and possibly therapeutic relevance for patients with SCLC.