Systemic retinoids are known to cause dryness of the mouth and changes in oral and lip mucosa. The purpose of this study was to evaluate changes in salivary variables during treatment with oral isotretinoin in patients receiving the drug for 3 months for cutaneous acne. Patients were examined 1 month after initiation of medication and approximately 3.7 months after its discontinuation. Salivary flow and pH could be measured in 8 and the relative amount of matrix metalloproteinase-9 (MMP-9) of stimulated saliva in 17 patients. The mean flow rate of stimulated saliva was lower during medication than at control examination (P = 0.0277), but no change in the mean pH value was observed during medication. The mean activity of MMP-9 during medication was higher than at control examination (P = 0.0442). The enzyme activity increased in 13 of 17 and decreased in 4 of 17 cases.