The purpose was to select drugs that specifically reduce collagen synthesis by palatal granulation fibroblasts without affecting their proliferation. Granulation fibroblasts were obtained from 8-day-old palatal mucoperiosteal wounds and normal fibroblasts from palatal tissue of unwounded rats. Cultured cells were treated with interferon-alpha2b, interferon-beta and interferon-gamma (0, 100, 1000, and 10000 U/ml). Cell proliferation was measured by [3H]thymidine incorporation. Collagen synthesis and non-collagenous protein synthesis were determined from the incorporation of [3H]proline. None of the interferons significantly inhibited the proliferation of either type of fibroblasts. Interferon-alpha2b had no effect on the variables studied at the dosages used. Interferon-beta reduced collagen synthesis of granulation fibroblasts without affecting their non-collagenous protein synthesis or protein synthesis by normal fibroblasts. Interferon-gamma reduced collagen synthesis of both types of fibroblast and the non-collagenous protein synthesis of granulation fibroblasts. These data show that interferon-beta specifically reduces collagen synthesis by oral granulation fibroblasts without affecting normal palatal fibroblasts.