Rats intravenously self-administer both optical isomers of amphetamine and methylamphetamine. Responding was maintained under a schedule where every lever-pressing response produced an intravenous drug injections. When self-administration was limited to 6 hour/day sessions, increases in dose produced decreases in response rate and relatively slight inereases in hourly drug intake. Responding was maintained by lower doses of the d -than of the l -isomer of both amphetamine and methylamphetamine. Responding resulted in 2.38 to 2.98 times more l -than d -amphetamine and 4.31 times more l -than d -methylamphetamine being self-administered per hour. At similar molar doses, 1.75 times more l -methylamphetamine than l -amphetamine was self-administered but no difference between d -amphetamine and d -methylamphetamine was found over the range of doses studied. When rats were allowed to self-administer drugs 24 hours/day at doses that produced equal response rates, qualitative effects were similar with both isomers of each drug: alternating periods of responding and no responding, weight loss, body irritation and typically death within two weeks. With onset of self-administration, responding maintained by food and water decreased while activity increased.