The spontaneous regression of melanoma in Sinclair miniature swine inv
olves the replacement of tumours by pigmented cells, hitherto interpre
ted as pigment-laden macrophages (PLMs). We hypothesized that these re
sidual cells are terminally differentiated melanoma cells, not monocyt
e-derived macrophages. Swine melanoma explants with no regression were
transplanted into severe combined immunodeficient (SCID) mice. Harves
ted transplant sites were examined by routine light and electron micro
scopy techniques. Paraffin sections were also stained with Hoeschst dy
e and examined by fluorescence microscopy. All but one site had comple
tely regressed and were replaced by PLM-like cells. Hoeschst staining
indicated they were of swine, not mouse, origin. The ultrastructural f
eatures of the single, partially regressed lesion demonstrated many pr
emelanosomes in these cells. We conclude that tumour differentiation i
s an important mechanism of regression in the Sinclair swine melanoma
model.