The incidence of abuse of pentazocine and tripelennamine (T's and Blues) suggests that the mixture has greater abuse potential than does either agent alone. Pentazocine (40 and 80 mg), tripelennamine (50 and 100 mg), alone and in combination, and placebo were administered in random order to volunteering experienced drug users. Pentazocine alone and tripelennamine alone were identified as opioids and produced euphoria. The large dose of pentazocine produced sedation and dysphoria. Pentazocine and tripelennamine both raised blood pressure; pentazocine constricted pupils, tripelennamine did not. The addition of 50 mg of tripelennamine increased the euphoric effects of pentazocine and attenuated the dysphoric effects seen at higher doses. Adding 100 mg of tripelennamine did not appreciably increase further the euphoric effects and did not alter the dysphoric effects of high doses of pentazocine. The combination significantly increased the systolic and diastolic blood pressure, and the increase was at least additive. In combination, pupillary constriction was slightly antagonized. These studies suggest that the antihistamine tripelennamine has abuse potential, and that in combination with pentazocine, the euphoric effects of the opioid are enhanced and its dysphoric properties attenuated.