A capillary cloning system for primary human tumor colony-forming units was applied to a total of 286 tumors, and 226 (79%) provided satisfactory cultures. These were used to study the in vitro anti-proliferative effects of a recombinant DNA human interferon-beta (rIFN-beta ser). Growth inhibition was somewhat greater when relatively high IFN concentrations were used, but continuous exposure to the IFN was not more effective than exposure for only 1 h. The tumors inhibited included breast, kidney, lung (non-small-cell), head and neck cancers, melanoma, and, especially, mesothelioma. This spectrum of activity differs from that of the IFNs-alpha so far examined. The IFN-beta ser did not differ significantly in activity from native IFN-beta. When tested in combination with five cytotoxic anticancer agents, it did not increase their effects. Future correlation of these in vitro data with clinical results will show whether this capillary cell cloning method is a useful predictor of antitumor activity in patients.