Staining for basic fibroblast growth factor (bFGF), a potent mitogen, was examined in muscle recovering from a crush injury and compared between two mouse strains with distinctly different capacities for muscle regeneration to determine if bFGF staining and the steps and outcome of repair were related. Immunofluorescence studies on intact and crushed tibialis anterior muscle were carried out at 0, 1, 3, 6, and 12 h postcrush in SJL/J mice, and at 1, 2, 3, 5, 7, and 11 days after injury in both SJL/J and BALB/c mice (n = 2-4). Disrupted fibers showed increased sarcoplasmic staining for bFGF as little as 3-6 h after injury prior to infiltration with intensely fluorescent mononuclear cells (at 12-24 h). Fiber bFGF was maintained in SJL/J muscles for 2 days, but was lower in most damaged fibers of BALB/c muscles at the same time. Surviving stumps of crushed fibers, once sealed, exhibited sarcoplasmic extensions, some of which stained intensely for bFGF. These processes appeared to connect adjacent fiber stumps, and many were noted in association with aligned mononuclear cells (presumptive myoblasts) at the site of new myotube formation. In representative sections there were more bFGF-positive mononuclear cells present in SJL/J than BALB/c muscles. Intense bFGF localization marked newly regenerating myotubes in both SJL/J and BALB/c muscles, and such myotubes were more frequent and larger in SJL/J muscles. More bFGF was present in regenerating muscles of SJL/J compared with BALB/c mice (with respect to damaged myofibers, mononuclear cells, and myotubes) and this correlates with the superior new muscle formation seen in SJL/J mice. These studies support the idea of a positive relation between bFGF in damaged fibers, the bFGF-positive mononuclear cells, and the speed and success of muscle regeneration.