Purpose: To investigate an association of the severity of the human immunodeficiency virus (HIV) disease with decreased tear production in a controlled setting. Patients and Methods: Seventy-two patients (144 eyes) and 30 age- and sex-matched control subjects (60 eyes) were studied prospectively. Tear production was measured using the Schirmer I test (measured in millimeters after 5 minutes). Patients were classified into three clinical groups: asymptomatic HIV infection, lymphadenopathy syndrome (LAS) or acquired immune deficiency syndrome (AIDS)-related complex (ARC), and AIDS. Additionally, patients were classified according to the CD4+ lymphocyte count. Results: Tear production (mean +/- standard deviation) did not differ (P = 0.32) among eyes of patients with asymptomatic HIV infection (17.1 +/- 10.8; n = 14), LAS or ARC(18.3 +/- 10.3; n = 70), and AIDS (20.7 +/- 10.3; n = 60). In addition, mean tear production was not decreased significantly when comparing each clinical group with the control subjects(17.8 +/- 4.4). However, the relative frequency of eyes with significantly decreased tear production (<9 mm) was 23.6% in all 144 eyes. In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.52) between eyes of patients with asymptomatic HIV infection (35.7%), LAS or ARC (21.4%), and AIDS (24.1%). In addition, the relative frequency of significantly decreased tear production did not differ (P = 0.30) between eyes of patients with a CD4+ count of more than 400 cells/mu l (23.1%; n = 26), 400 to 200 cells/mu l (31.3%; n = 48), 200 to 50 cells/mu l (14.3%; n = 42), and less than 50 cells/mu l (21.4%; n = 28). Conclusion: The authors data show that decreased tear production occurs in approximately 20% to 25% of patients with HIV infection. This increased frequency of decreased tear production is not associated with the CD4+ count, or related to the severity of HIV disease, respectively. The possibility of an autoimmune-like pathogenesis of abnormalities of tear production in patients with HIV infection should be studied intensively.