In human immunodeficiency virus (HIV) disease, symptoms of underlying illness may promote weight loss through decreased caloric intake, increased metabolic needs, or nutrient malabsorption. We evaluated disease symptoms as predictors of acute weight loss (i.e., loss of > or =5% of weight). HIV-infected men and women (n=415) were telephoned every 5 weeks to obtain information about weight and recent symptoms. Weight change between each pair of consecutive calls (telephone intervals, 2814) was calculated. Acute weight loss occurred across 4.5% of intervals and among 24% of individuals. Patients reported > or =1 symptom before 58% of telephone intervals. The most common symptoms or symptom complexes before intervals were diarrhea (21% of patients), anorexia (17%), upper respiratory symptoms (16%), skin symptoms (12%), and abdominal pain (12%). Trouble swallowing (6%) and oral symptoms (7%) were less common. Risk of acute weight loss was significantly increased when oral symptoms or trouble swallowing were present, and it was decreased when highly active antiretroviral therapy (HAART) was used or when diarrhea was not present. Even when HAART is being administered, clinicians should remain vigilant regarding weight loss, oral symptoms, and trouble swallowing.