The chronic usage of nifedipine is associated with the appearance of gingival overgrowth (GO). The frequency of GO associated with chronic nifedipine therapy remains controversial and the possible subclinical effects of this drug on the gingival epithelium should be investigated. We investigated the epithelial proliferation index and apoptosis rate, and their association with epithelial enlargement. Proliferation (Ki67 and Cyclin B1) and apoptosis (BCL2, Bax and p53) markers were identified by immunohistochemistry in twenty-one samples of gingival tissue from patients undergoing chronic treatment with nifedipine and in eleven samples of gingival tissue from healthy patients who did not use drugs associated with GO (control). Our results show that the epithelial tissue of nifedipine users has considerably longer rete pegs compared to control (P = 0.01). However, the density of Ki67⁺ and Cyclin B1⁺ cells was similar in both groups. Regarding apoptosis, we found more BCL2⁺ cells in the nifedipine group when compared to controls (P = 0.12). An increase in Bax⁺ cells in the nifedipine group compared to control (P = 0.003) was also seen, and slightly lower levels of p53⁺ expression were observed (P = 0.51). Our results suggest that the chronic use of nifedipine is not associated with subclinical changes in gingival tissue. (J Oral Sci 52, 55-62, 2010)