Inositol, an isomer of glucose and precursor in the phosphatidylinositol cycle, may be effective in a number of psychiatric disorders, including obsessive-compulsive disorder (OCD). There is little data, however, on inositol as an augmenting agent of serotonin reuptake inhibitors (SRIs) in treatment-refractory patients. Ten OCD patients who had failed to respond to current and previous trials of serotonin reuptake inhibitors participated in open-label trial of inositol (18 gm/day) [corrected] augmentation for 6 weeks. Symptoms were rated at 2-weekly intervals using the Yale-Brown Obsessive-Compulsive Scale, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impressions (CGI) Scale. The majority of patients (n = 7) did not respond to treatment with inositol augmentation on the CGI improvement item. However, a small number of patients (n = 3) did report a clinically significant response on the CGI improvement item. OCD patients who fail to respond to a number of trials of SRIs may be a particularly treatment-refractory group of subjects. Unfortunately, inositol augmentation of a SRI did not lead to significant improvement in the majority of such cases. Nevertheless, further research on the mechanism of inositol efficacy in some patients with anxiety and mood disorders is warranted.