The relative efficacy of conventional treatment alternatives that are routinely used to treat acutely relapsed schizophrenic patients who have failed an initial course of standard neuroleptic therapy has not been adequately studied, nor have predictors of poor treatment response been reliably identified. We have recently reported preliminary findings that suggest that these patients may subsequently fail to respond to such conventional alternative treatments as (1) maintaining the same dose of the neuroleptic over an extended trial, (2) significantly increasing the dose of the same neuroleptic, or (3) switching to a different class of neuroleptic. Negative symptoms and acute extrapyramidal side effects (EPS) evident during the initial treatment trial were associated with a less favorable clinical response to neuroleptic treatment. We now report on the association between clinical response and negative symptoms and acute EPS. Present findings suggest that a particular degree of negative symptoms apparent prior to treatment may be associated with a poor subsequent treatment response and that negative symptom scores and EPS ratings demonstrate a significant correlation with severity of psychiatric ratings during the treatment trial. The relationship among neuroleptic resistance, negative symptoms, and acute EPS requires further study.