Catecholamine levels in frontal cortex were determined in vivo by electrochemical detection after the local application of dopamine (DA) from multibarrel micropipettes by pressure ejection or microiontophoresis. Tissue DA levels were linearly related to microapplication doses with either technique and reached steady state with longer application times. Furthermore, the plateau DA tissue concentrations were clearly related to ejection pressure or iontophoretic current. Using either microapplication technique, the tissue DA levels decreased as distance between the recording electrode and the tip of the drug pipette increased. However, pressure ejected and iontophoretically applied drug differed in their concentration versus time dynamics. Thus, although similar tissue concentrations of drug can be generated by the two techniques, the time dynamics of the drug effects may not be comparable. The quantitative use of these drug application techniques requires a minimal amount of variance in release between pipettes in order to effectively measure small sensitivity differences. Although the 10-fold variance with microiontophoresis does not appear resolvable at present, improved pipette construction techniques permit the variability in dosage to be limited to a maximum of 3-fold with pressure ejection. In addition, the present data also suggest that this variance can be further minimized by holding either ejection duration or ejection pressure constant when establishing dose-response relationships.