The early course of neuropsychological dysfunction in schizophrenia and the impact of treatment on these deficits need to be better specified. A sample of 45 patients with schizophrenia underwent five neuropsychological evaluations from prior to treatment with antipsychotic treatment through a 2-year follow-up period. A comparison sample of 33 matched healthy individuals underwent neuropsychological evaluations at similar time points. At baseline, a generalized deficit across cognitive domains was evident for the schizophrenia sample. After 6 weeks of treatment, patients showed modest improvements in visual memory and visual perception, but a decline in verbal memory. Verbal memory performance returned to baseline levels by the 6-month follow-up while deficits in other neuropsychological domains persisted throughout the 2-year period. Relatively static and generalized neuropsychological dysfunction, evident from illness onset, is consistent with neurodevelopmental rather than neurodegenerative models of schizophrenia.