Voltammetry has been widely used in attempts to measure catecholamine release in vivo. The voltammogram recorded in the rat striatum using carbon paste electrodes and linear sweep voltammetry with semidifferentiation consists of a number of separate peaks; changes in the height of the first of these peaks have been attributed to changes in catecholamine release. We have found that ascorbate, either microinjected into the striatum or injected intraperitoneally, increases the height of the first peak without changing its potential. Microinjection of dopamine or 3,4-dihydroxyphenylacetic acid, or intraperitoneal injection of 3,4-dihydroxyphenylalanine, caused a shift in the potential of peak 1 of 25-50 mV in a positive direction. Amphetamine, administered intraperitoneally to freely moving animals, caused an increase in the height of the first peak but did not change its potential. Oxidation potentials in vitro and the effect of other drugs on the voltammogram obtained in vivo were also measured. Peak 1 is caused by the oxidation of both ascorbate and catechols whose oxidation potentials differ by only 50 mV in vivo; the contribution of catechols in control animals is negligible. Shifts in the potential of peak 1 caused by drugs are not due to changes in the oxidation potentials of the components but to a change in their relative contributions. Therefore changes in the height of peak 1 with no change in position do not represent changes in the extracellular concentration of catechols but are due to changes in ascorbate concentration. Changes in the concentration of catecholamine-related compounds can be detected at potentials some 50 mV greater than that of the first peak.