The lateralized readiness potential (LRP) is an electrophysiological indicator of the central activation of motor responses. Procedures for deriving the LRP on the basis of event-related brain potential (ERP) waveforms obtained over the left and right motor cortices are described, and some findings are summarized that show that the LRP is likely to reflect activation processes within the motor cortex. Two experiments investigating spatial S-R compatibility effects are reported that demonstrate that, because of systematic overlaps of motor and nonmotor asymmetries, LRP waveforms derived by the double subtraction method cannot always be interpreted unequivocally in terms of response activation. Such confounds can be detected when LRP waveforms are compared with difference waveforms obtained by the double subtraction method from ERPs elicited at other lateral scalp sites.