Interleukin-2 and interleukin-12 have been used independently to successfully treat the induced and the spontaneous tumours in animals. This trial was done to determine if a combination of IL-2 and IL-12 in the treatment of spontaneous bovine ocular squamous cell carcinomas (BOSCC) would be more successful than IL-2 or IL-12 therapy by themselves. For this trial, we selected 25 BOSCC tumours seen on Holstein Fresian cows in Beatrice, Zimbabwe. The cows were randomly assigned to a treatment group of 5 days of IL-2 (200,000 U/day), 5 days of IL-12 (0.5 microg/day) or 5 days of IL-2 (200,000 U/day) and IL-12 (0.5 microg/day). At 20 months after treatment, the IL-2 therapy group had 63% complete regressions; the combination group had 38% complete regressions, which were significantly higher than the IL-12 group, which had 0% complete regressions at 20 months, despite having 29% complete regressions at 6 months. These results show that IL-2 therapy by itself and in combination with IL-12 is more successful than IL-12 by itself. However, combination therapy does not improve the outcome in comparison to IL-2 as a single therapy. It also proves that IL-2 is consistently successful in the therapy of BOSCC with over 60% complete regression, which corresponds to a number of other studies we have done on IL-2 therapy of BOSCC [Rutten, V.P.M.G., Klein, W.R., De Jong, W.A., Misdorp, W., Den Otter, W., Steerenberg, P.A., De Jong, W.H., Ruitenberg, E.J., 1989. Local interleukin-2 therapy in bovine ocular squamous cell carcinoma. A pilot study. Cancer Immunol. Immunother. 30, 165--169; Stewart, R.J.E., Hill, F.W.G., Masztalerz, A., Jacobs, J.J.L., Koten, J.W., Den Otter, W., 2003. Local low dose interleukin-2 therapy of bovine ocular squamous cell carcinomas in cattle in Zimbabwe, submitted for publication; Den Otter, W., Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder, P.H.M., Rutten, V.P.M.G., Ruitenberg, E.J., 1993. Low doses of interleukin-2 can cure large bovine ocular squamous cell carcinoma. Anticancer Res. 13, 2453-2455; Den Otter, W., Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder, P.H., Rhode, C., Stewart, R., Faber, J.A., Ruitenberg, E.J., 1995. Therapy of bovine ocular squamous cell carcinoma with local doses of interleukin-2: 67% complete regressions after 20 months of follow-up. Cancer Immunol. Immunother. 41, 10-14].