The term Excitation-Coupled Ca2+ Entry (ECCE) designates the entry of extracellular Ca2+ into skeletal muscle cells which occurs in response to prolonged depolarization or pulse trains, and which depends on the expression of both the 1,4-dihydropyridine receptor (DHPR) and the type 1 ryanodine receptor (RyR1). The ECCE pathway is blocked by pharmacological agents that also block store-operated Ca2+ entry, is relatively insensitive to nifedipine (1 μM), and is permeable to Mn2+. We have examined the effects of these agents on the L-type Ca2+ current conducted via the DHPR. We found that the non-specific cation channel antagonists 2-APB, SKF 96356, La3+ and Gd3+ all inhibited the L-type current. In addition, complete (>97%) block of the L-type current required concentrations of nifedipine >10 μM. Like ECCE, the L-type channel displays permeability to Mn2+ in the absence of external Ca2+ and produces a Ca2+ current that persists during prolonged (∼10 s) depolarization. This current appears to contribute to the Ca2+ transient observed during prolonged KCl-evoked depolarization of intact myotubes because (i) the transients in normal myotubes decayed more rapidly in the absence of external Ca2+, (ii) the transients in dysgenic myotubes expressing SkEIIIK (a DHPR α1S subunit pore mutant thought to conduct only monovalent cations) had a time course like that of normal myotubes in Ca2+-free solution and was unaffected by Ca2+ removal, and (iii) after block of SR Ca2+ release by ryanodine, normal myotubes still displayed a large Ca2+ transient whereas no transient was detectable in SkEIIIK-expressing dysgenic myotubes. Altogether, these results indicate that the skeletal muscle L-type channel is a major contributor to the Ca2+ entry attributed to ECCE. Supported by NIH NS24444 and AR44750 to K.G.B., and MDA 4155 to R.A.B.