Objective:To evaluate the effects of an oral nutritional supplement enriched with two potentially immunostimulant compounds (arginine and Ω-3 fatty acids) on the changes in food intake, body composition, immune parameters and viraemia in HIV-infected outpatients.Design:Six-month prospective randomized double-blind controlled study.Setting:University hospital outpatient nutrition clinic.Patients:Sixty-four HIV-infected outpatients with CD4 lymphocyte count ≥ 100 × 106/l.Intervention:All patients received a daily oral nutritional supplement (606 kcal supplemented with vitamins, trace elements and minerals). In addition, half of the patients were randomized to receive 7.4 g arginine plus 1.7 g Ω-3 fatty acids.Main outcome measures:Disease progression measured by AIDS-defining events, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors, nutritional status determined by anthropometric, bioelectrical impedance and dietetic assessment.Results:Fifty-five patients completed the protocol. Compliance with and tolerance of oral nutritional supplement during the 6-month period was excellent. In both groups of patients the following were found: total energy intake was transiently increased and then returned to baseline level; nitrogen/energy intake ratio was increased throughout the study; gain of body weight and fat mass were approximately 2 and 1 kg, respectively, over 6 months, and were similar in both groups. In addition, CD4 and CD8 lymphocyte counts, viraemia, tumour necrosis factor soluble receptors remained statistically unchanged and were similar in both groups.Conclusions:Enrichment of an oral nutritive supplement with arginine and Ω-3 fatty acids did not improve immunological parameters. However, body weight increased in both groups.