The mechanism of gingival overgrowth associated with long-term use of nifedipine and of other drugs that affect calcium homoeostasis, such as cyclosporin and phenytoin, is unknown. With an ultrasensitive assay, we measured the pharmacokinetics of nifedipine in plasma and gingival crevicular fluid (GCF) of nine patients receiving this drug for angina and hypertension. In seven patients, the maximum nifedipine concentration was in the range 15-316 (mean 84 [SD 105]) times greater in GCF than in plasma. The two patients with low (undetectable) GCF nifedipine did not have overgrowth. We propose that gingival tissues sequester nifedipine and that the very high nifedipine concentrations predispose the tissues to overgrowth.