Thirty patients with metastatic colon or breast cancer were treated with recombinant alpha-interferon, clone A, 9 to 50 X 10(6) units/sq m, i.m., 3 times weekly for up to 4 months. Immunological parameters including natural killer activity, antibody-dependent cellular cytotoxicity, an assay of inhibition of tumor cell growth in culture, and quantification of leukocyte subsets were monitored serially. Statistically significant increases in the inhibition of tumor growth and in the proportion of peripheral blood mononuclear cells bearing the T10 marker were observed both early and late in the treatment course in the population as a whole (p less than 0.03 and p less than 0.0001, respectively). The true maximum effect in the assay of inhibition of tumor growth was probably higher, since the monitoring was not performed at peak activity for this assay. Other immune parameters, including natural killing, could not be shown to change consistently in the population as a whole, although interferon effects could be discerned easily in the activity profiles of some individual patients. The two patients with tumor response showed increased putative tumor immunity by these measures. These data confirm results previously published supporting the responsiveness of these parameters to interferon as administered clinically and may provide the basis for optimization of interferon dose and scheduling.