Serum levels of haloperidol (HPL) and reduced haloperidol (RHPL) as well as the RHPL/HPL ratio were determined in 55 acute schizophrenics on oral haloperidol medication and correlated over 28 days with psychopathology and extrapyramidal symptom scores. Linear and nonlinear models of serum concentration and psychopathology were tested at several time points. No single consistent model could be established for either HPL or RPHL. However, when non-parametrical methods are used HPL levels between 10 and 25 ng/ml can be shown to be significantly associated with better outcome during the first three weeks of treatment. RHPL is unsuitable for therapy monitoring, since equilibrium is not reached in the first four weeks of treatment. The RHPL/HPL ratio was found to rise continuously during the study, and it neither separated responders from nonresponders nor did it correlate with clinical outcome.