Objective. To assess the influence of the menstrual cycle and oral contraceptives on pain sensitivity and local anesthetic effectiveness. Study design. Thirty volunteers were designated into 3 groups (n = 10): group 1, women using contraceptives; group 2, women not using contraceptives; and group 3, men. Groups 1 and 2 had a buccal infiltration of 2% lidocaine with 1:100,000 epinephrine at the upper-right canine during each one of the 5 phases of the menstrual cycle and group 3 at a randomly selected day. Pain threshold, latency period, and pulpal anesthesia were measured with an electrical pulp tester. Injection discomfort was recorded. Data were analyzed with Friedman and Kruskal-Wallis tests. Results. Pain threshold was higher in men; however, there were no significant differences (P > .05) in anesthetic duration and injection discomfort. Conclusion. Injection discomfort and clinical effectiveness of local anesthetics are not related to sex, phases of the menstrual cycle, or use of oral contraceptives.1032E34E38