Human lymphocytes were derived from the spleen of a 15-year-old female patient after partial splenectomy. High cell yield and percentage of human B-lymphocytes (over 30%) gave useful conditions for their fusion to mouse myeloma cells (P3 X63/Ag8/653). Fusion efficiency (cultures with growth) was 96%. From 288 initially seeded cultures 176 showed IgM and only one IgG production as determined by enzyme immunoassays. Twenty primary cell lines were cloned with differing results and 17 heterohybridoma cell clones with high IgM production rates could be established for more than 6 months in vitro. The present results show the possibility to produce human monoclonal antibodies in heterohybrids derived from human spleen lymphocytes.