The goal of this study was to explore the relation between self-reported adherence to antiretroviral treatment and degree of sense of coherence in a group of human immunodeficiency virus (HIV)-infected patients. Ninety-nine patients from an outpatient clinic, all undergoing antiretroviral therapy, participated. Questionnaires were answered twice at a 12-month interval. The 29-item Sense of Coherence (SOC) Scale was used for measuring the ability to cope with stressful life situations. Medication adherence was assessed with self-reported measurements. Clinical characteristics and background variables were collected from the medical records. Results from variables measured with the 12-month interval show a significant concordance with disease stage (p < or = 0.0001), and in HIV-RNA copies per milliliter (p < or = 0.0001) and an increase in CD4 cell count/mm3 (p = < 0.0001). Univariate analysis showed significant differences between nonadherent patients (n = 19) and adherent patients (n = 80) at the last measurement (i.e., the nonadherent group had lower CD4 cell count/mm3 [p = 0.004], higher HIV-1 RNA levels [p 50.029], and lower SOC [p = 0.04] than the adherent group). Finally, multiple regression analyses showed that at measurement 2 the SOC predicted nonadherence, the lower SOC the more missed doses (p < or = 0.01). Because SOC seems to play an important role in this group of patients managing their disease, a caring patient-provider relationship should be developed to minimize nonadherent behaviour. For this reason SOC scale might be of great clinical value to identify patients needing the most support for successful treatment.