Spleen cells from 6-day-old nonimmunized BALB/c and BALB.B10 mice were fused with the nonsecreting hybridoma cell line Sp2/0. Three hundred and eighty-four immunoglobulin-secreting hybrids were screened for antibody activity against mouse actin, tubulin, and myosin, and against TNP, peroxidase, renin, DNA, and neurofilaments. At least 24 hybridomas in the collection (6.25%) exhibited antibody activity against this panel of antigens. Ten of these hybrids were cloned, were propagated, and the corresponding monoclonal IgM protein was isolated from ascitic fluids and was further characterized. At least four groups of antibody specificities were identified: 1) one clone reacting with TNP only; 2) one clone reacting with both actin and tubulin; 3) two clones which bound to both TNP and actin; and 4) a fourth group, comprising the six other clones, which all exhibited widespread reactivity and bound to actin, tubulin, myosin, and TNP. These results indicate: 1) B cell clones directed against self antigens are activated in the internal environment and are recovered consequently by somatic cell hybridization; 2) the widespread antibody specificities found for these newborn mouse antibodies are very similar to those previously characterized with human natural antibodies and human monoclonal Ig; and 3) the frequency of B cells binding to cytoskeletal proteins and TNP is very high (at least 6.25%).