Twenty-two patients with measurable metastatic renal carcinoma were treated with human alpha lymphoblastoid interferon (Wellferon) (3 million units/m2 of body surface area) im three times a week for 6 weeks; 21 were evaluable for response and toxicity. One patient had a partial regression of disease lasting 39 weeks and another had a minor response. Six patients had partial or minor response in one area but no change in the disease elsewhere (mixed response); they were classified as having stable disease. An additional seven patients had no change in measurable disease and in six the disease progressed. The tumor regressions by metastatic site were four of 14 patients, pulmonary; three of four, soft tissue; one of nine, bone (? soft tissue); none of three, mediastinal; none of four, renal; none of five, liver; and none of ten, other abdominal sites of tumor. The side effects were fever (101 degrees F-103 degrees F), chills, malaise, anorexia, minor (10%-20%) decrease in performance status, and weight loss. We concluded that interferon had some activity against metastatic renal carcinoma, although clinically useful responses were quite infrequent. While lung metastases appeared to be more responsive than those at other sites, careful examination of the data suggests that this simply reflects differences in the bulk of the metastatic disease. Smaller metastases appear more likely to respond than bulky metastases.