Conjunctival pigmented lesions, including ten compound nevi, three subepithelial nevi, two acquired melanoses, and six melanomas, were examined histologically and immunohistochemically to determine the specificity of mouse monoclonal HMB-45 antibody for these lesions. Eleven of 13 nevi, two of two acquired melanoses, and six of six melanomas stained with this antibody. Conjunctival melanomas showed intense and diffuse cytoplasmic staining; compound nevi and subepithelial nevi showed less intense but diffuse reaction. There was strong staining in melanocytic cells at the junction of the epithelium and substantia propria in compound nevi and acquired melanoses. Unlike skin nevi, conjunctival nevi show HMB-45 reactivity in their stromal components. Immunoreactivity to HMB-45 does not distinguish benign from atypical or malignant melanocytic lesions of the conjunctiva.