The relationship between plasma concentration, clinical outcome and side-effects was examined in 23 patients with major depressive disorder (DSM-III-R) treated with fluoxetine. All patients received a fixed dose of 20 mg for 6 weeks. Good response was observed in 57% of patients, while 30% of patients had moderate responses after 6 weeks of treatment. Fluoxetine and norfluoxetine plasma concentrations were not significantly influenced by age and sex. At 6 weeks, plasma fluoxetine concentrations were not significantly different between responders and non-responders to treatment (82.2 +/- 59.6 micrograms/l vs. 84.7 +/- 6.7 micrograms/l) or those with or without side-effects (74.6 +/- 28.7 micrograms/l vs. 87.0 +/- 66.6 micrograms/l). Similarly, norfluoxetine concentrations were not significantly different for responders and non-responders (65.5 +/- 28.9 micrograms/l vs. 66.5 +/- 26.2 micrograms/l) or those with or without side-effects (66.6 +/- 14.4 micrograms/l vs. 61.5 +/- 33.6 micrograms/l). Plasma concentrations and clinical outcome were not related in a simple manner. Further studies are needed to evaluate the role of monitoring plasma fluoxetine/norfluoxetine concentrations as a routine procedure.