During the formation of skeletal muscle, secondary fibres form, by cell fusion, on the surface of primary fibres. Three-dimensional reconstructions of primary fibres with the secondary fibres and cells on their surfaces were produced from spaced serial transmission electron micrographs. Reconstructions were made of fibres from embryonic day (E) 17, E19, and E21 of the Extensor Digitorum muscle of Balb/c mice. Cell distribution was analysed in two ways. Firstly, nearest neighbour analysis was used to see if cells were randomly arranged or clustered. Secondly, the association of cells and secondary fibres was tested by measuring the distances between cells and each secondary fibre. Cells were found to be randomly distributed on the surface of primaries at E17 but significantly clustered, and associated with smaller secondary fibres at E19 and E21. Cells were not associated with the ends of secondary fibres. Cells associated with secondary fibres lay in the groove formed by contact between adjacent primary and secondary fibres. This apparent response to the topography of the surface on which the cells are lying has previously been mimicked in vitro by growing cells on grooved surfaces. It is likely that cells associated with secondaries will fuse laterally with these fibres and their response to topography is part of the process of bringing them into correct alignment with the fibre before fusion.