Two intralesional injections of interferon alfa-2b (1.5 million U per injection) into a progressively enlarging keloid resulted in a 41% reduction in its area. Fibroblasts cultured from the keloid before and 9 days after the initial injection were compared with fibroblasts cultured from the patient's normal skin with respect to proliferation and production of connective tissue matrix components and collagenase. There were no significant differences in the in vitro doubling times of keloidal fibroblasts before (p > 0.2) and after (p>0.5) treatment with interferon alfa-2b, as well as of normal fibroblasts, in subconfluent cultures. Multiple passages of keloidal fibroblasts before interferon alfa-2b therapy assayed as confluent cultures produced more collagen (171%, 187%, and 204%), more glycosaminoglycans (153% and 141%), and less collagenase (26% and 31%) than the patient's own normal fibroblasts. In contrast, keloidal fibroblasts after interferon alfa-2b therapy persistently produced normal or subnormal amounts of collagen (107%, 73%, and 64%) and glycosaminoglycans (97% and 96%) and normalized levels of collagenase activity (96% and 86%). Normal amounts of fibronectin were produced by keloidal fibroblasts before and after treatment with interferon alfa-2b.