The signal-transduction mechanism of rhodopsin was studied by molecular dynamics (MD) simulations of the high-resolution, inactive structure in an explicit membrane environment. The simulations were employed to calculate equal-time correlations of the fluctuating interaction energy of residue pairs. The resulting interaction-correlation matrix was used to determine a network that couples retinal to the cytoplasmic interface, where transducin binds. Two highly conserved motifs, D(E)RY and NPxxY, were found to have strong interaction correlation with retinal. MD simulations with restraints on each transmembrane helix indicated that the major signal-transduction pathway involves the interdigitating side chains of helices VI and VII. The functional roles of specific residues were elucidated by the calculated effect of retinal isomerization from 11-cis to all-trans on the residue-residue interaction pattern. It is suggested that Glu134 may act as a "signal amplifier" and that Asp83 may introduce a threshold to prevent background noise from activating rhodopsin.