Summary Polyclonal anti-idiotypic antibodies (ab2) were generated by immunising goats with the murine IgG2a monoclonal antibody SWA20 which recognises the SCLC antigen cluster-SA, a tumour-associated sialoglycoprotein. Ab2 was shown to bind specifically to antibody SWA20, but not to isotype matched control antibodies. Pre-incubation with ab2 completely inhibited target cell binding of antibody SWA20 and of four other antibodies to cluster-5A antigen, while no effect was seen with antibodies to cluster-I and cluster-w4 antigen. By these criteria the ab2 population consists of antibodies resembling in their reactivity pattern the cluster-5A antigen. Ab2 was used for immunisation of rabbits and two strains of mice; control animals received PBS or nonspecific goat IgG. Anti-anti-idiotype sera (ab3) were analysed in a series of radioimmunoassays for reactivity with goat IgG and reactivity with ab2. After blocking the nonspecific anti-goat response, ab3 could be shown to bind specifically to ab2 idiotype. As (Forstrom et al., 1983;Kennedy et al., 1985), mouse mammary carcinoma (Gorczynski et al., 1984), rat sarcoma (Dunn et al., 1986), and mouse lymphoma . Anti-idiotypic antibodies to murine monoclonal antibodies recognising surface antigens of human tumours have been developed in several antigenic systems, including the melanoma antigen p97 (Nepom et al., 1985), gastric carcinoma antigen GA733 (Herlyn et al., 1985), colon carcinoma antigen 17-lA (Herlyn et al., 1987), and a high molecular weight melanoma antigen (Kusama et al., 1989). In the latter two systems, results of the clinical use of anti-idiotypic antibodies have been published. The studies have demonstrated that anti-idiotypic antibodies can be safely administered and that an anti-anti-idiotypic (ab3) response can be obtained in the majority of patients (Herlyn et al., 1987;O'Connell et al., 1989). Occasional clinical responses occurred, but due to the design of the studies cannot yet be attributed with certainty to an immune response against the tumour-associated antigens elicited by the administration of anti-idiotypic antibodies.We have previously identified two tumour-associated sialoglycoprotein antigens given the workshop designation cluster-5 and cluster-SA which are strongly expressed on a proportion of small cell lung carcinomas (SCLC) and are virtually absent from normal adult tissues (Stahel et al., 1987;Waibel et al., 1988