Although skeletal muscle abnormalities have been described in association with human immunodeficiency virus (HIV), the effects of HIV infection on respiratory muscle function have not been well characterized. We hypothesized that HIV+ individuals may develop respiratory muscle weakness and that respiratory muscle dysfunction may contribute to the unexplained dyspnea that occurs in the setting of HIV. To test this hypothesis we studied maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), inspiratory muscle endurance, and respiratory symptoms in 23 HIV+ male outpatients who had no history of acquired immune deficiency syndrome (AIDS)-related pulmonary complications, with a CD4+ T-lymphocyte count of 331.6 +/- 62.1 (mean +/- SEM). Respiratory muscle endurance was measured with an incremental threshold loading (ITL) protocol. We compared these results to those for 14 HIV- males matched for age and weight. Compared with the controls, HIV+ subjects had a significantly lower mean MIP (98.7 +/- 7.4 versus 121.4 +/- 9.3 cm H2O, p < 0.05) and MEP (115.0 +/- 9.3 versus 152.1 +/- 14.8 cm H2O, p < 0.05). Furthermore, during ITL, the mean load at task failure in the HIV+ group was 295.7 +/- 36.2 g, versus 405.8 +/- 52.2 g in the control group (p < 0.05). In the HIV+ subjects there was no relationship between muscle performance and CD4+ count or azidothymidine (AZT) use. There was, however, a highly significant relationship between respiratory muscle dysfunction and symptoms of dyspnea. We conclude that HIV seropositivity is associated with a decline in respiratory muscle performance. This impairment in respiratory muscle function may contribute to the feeling of breathlessness that has been well described in this patient population.