Normal epidermal melanocytes are stimulated in vitro by fibroblast- and keratinocyte-derived growth factors. In this work, the paracrine responsiveness of human melanoma cells was investigated by cocultivation with growth-inhibited 3T3 fibroblasts. In short-term assays (3-4 days), melanoma cell growth was found to be improved if the cells were plated onto half-confluent 3T3 cell monolayers. In contrast, long-term cocultivation (greater than 7 days) resulted in significant growth inhibition of melanoma cells. These phenomena were not observed when melanoma cells were grown in 3T3 cell supernatants, which suggests a possible mediation by extracellular matrix components and/or by heterologous junctional communications.