The objective of the present study was to investigate the possibility of using L-lysine, an amino acid that occurs naturally in food and which interferes with nitric oxide (NO) production, for the treatment of schizophrenia. L-lysine, 6 g/day, was administered to ten patients with schizophrenia as an add-on treatment to conventional antipsychotic treatment. The study was designed as a single-blinded, cross-over study where patients were randomly assigned to initial treatment with either L-lysine or placebo and screened at baseline, after four weeks when treatment was crossed over, and after eight weeks when treatment was terminated. The four-week L-lysine treatment regimen caused a significant increased in blood concentration of the amino acid and was tolerated well. The analysis of outcome measures showed a significant decrease in symptom severity as measured by the Positive and Negative Syndrome Scale (PANSS). Furthermore, the patient's ability to solve the Wisconsin Card Sorting Task (WCST) was significantly improved indicating increased problem solving capacity and cognitive flexibility. Subjective reports from three of the patients also indicated decreased symptom severity and enhanced cognitive functioning. In summary, these findings suggest potential beneficial effects of L-lysine treatment on symptom severity and cognitive deficits in patients with schizophrenia.