Gingival overgrowth is a disfiguring condition affecting 10-20% of patients on nifedipine therapy. The pathogenesis of this condition, although unclear, is thought to involve an interaction between the drug and resident gingival fibroblasts. The aim of the present study was to investigate the cellular mechanisms underlying this condition using cell culture techniques. Gingival fibroblast cell lines were derived by explant culture from two patients on long-term nifedipine therapy exhibiting gingival overgrowth ('responders') and from two patients on similar therapy with clinically healthy gingiva ('non responders'). Comparative studies showed phenotypic differences between the two cell types, 'responder' cells having an increased growth potential and producing increased levels of protein and collagen compared to 'non responder' lines. Addition of exogenous nifedipine (10-1000 ng/ml) to cultures had no effect on 'non-responder' cells but induced a significant inhibitory response in the 'responder' cells. Although adding support to the concept that nifedipine-sensitive fibroblasts reside within overgrown connective tissue, the inhibitory effect of the drug on cell growth and matrix synthesis was surprising in view of the clinical appearance of this condition.