Cyclin D3, a cell cycle regulator, is encoded in the 6q21 chromosome region. Abnormalities of this gene and its protein product have not been found in normal tissues or in malignancies from human subjects. The expression of cyclin D3 was studied immunohistochemically in archival formalin-fixed, paraffin-embedded specimens from normal organs obtained from three autopsy cases and 237 human primary pulmonary carcinomas. In normal organs, nuclear positivity for cyclin D3 was observed in reactive type-2 pneumocytes, islets of Langerhans, lymphocytes from lymph nodes, superficial cells of transitional epithelium, epithelium of oesophagus, stomach, small intestine and gallbladder, endothelium, smooth muscles, and brain. Proliferating cells such as lymphocytes in the germinal centres and non-proliferating cells such as neurons both demonstrated cyclin D3 immunoreactivity. Cyclin D3 showed obvious nuclear immunoreactivity in 168 pulmonary carcinomas (71%). The proportion of tumour cells that were cyclin D3-positive ranged from 1% to 73% (median, 16%). There was no relationship between cyclin D3 immunoreactivity and histological typing, tumour differentiation, or pathological TNM staging. In pulmonary carcinomas, distinct expression of the cyclin D3 protein is unlikely to be implicated in tumorigenesis, because of its expression in only a small fraction of cancer cells. It may relate to cancer progression. The distribution of cyclin D3 reactivity in the normal tissues suggests that cyclin D3 affects other processes than cell cycle regulation in a lineage-specific manner.