In order to elucidate the interactions between fibroblasts and keratinocytes co-cultured in vitro, the morphology and growth of rat keratinocytes cultured with and without a feeder layer were compared. Morphological analysis was coupled with a simple morphometric method of image analysis performed with a computer aided system to demonstrate statistically significant differences between keratinocyte cultures obtained with and without a feeder layer. Epidermal cells cultured without fibroblasts but with a conditioning medium showed a slower growth rate and significant a greater cellular dimensions in comparison with cells grown in the presence of a feeder layer. These results suggest that the conditioning medium induces a morphological change of keratinocytes. The electrophoretic patterns of proteins extracted from cells cultured with and without a feeder layer were identical, whereas densitometric analysis revealed that the quantitative expression of proteins was clearly different. These data confirm that of keratinocyte growth is dependent on fibroblasts or fibroblast products.