Hemidesmosomes are junctional complexes involved in the attachment of epidermal basal keratinocytes to the basement membrane. To try to understand better the sequence of events in the morphogenesis of hemidesmosomes, we undertook an ultrastructural analysis of hemidesmosome formation in fetal and neonatal digit skin. Hemidesmosomes, defined as membrane-associated densities or plaques, were counted and scored for three morphological characteristics: (1) the presence of a sub-basal dense plate, (2) association with anchoring filaments within the lamina lucida and (3) contacts with intermediate filaments. No hemidesmosomes were evident at 7 weeks' gestational age. Between 9 and 15 weeks the number of hemidesmosomes increased by about fourfold (from 20.6 +/- 3.8 (SD) to 95.5 +/- 8.4 per 40 micro m of basal cell plasma membrane; P < 0.01). The association of hemidesmosomes with intermediate filaments and anchoring filaments also increased after 15 weeks (P < 0.05). Early attachment plaques first appeared as triangular focal densities on the basal plasma membrane with the appearance of sub-basal dense plates, which later became both larger and more electron dense. By 15 weeks, an inner plaque could be distinguished from the outer plaque, which coincided with a closer association with intermediate filaments. Hemidesmosomes appeared fully developed by 15 weeks' gestation. This study illustrates the structural relationship of hemidesmosomes to both intra- and extracellular filaments, suggesting close functional interactions. The complexity of the hemidesmosome plaque is also revealed early during development.