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Brain activity in humans telling lies has yet to be elucidated. We developed an objective approach to its investigation, utilizing a computer-based interrogation and fMRI. Interrogatory questions probed recent episodic memory in 30 volunteers studied outside and 10 volunteers studied inside the MR scanner. In a counter-balanced design subjects answered specified questions both truthfully and with lies. Lying was associated with longer response times (p < 0.001) and greater activity in bilateral ventrolateral prefrontal cortices (p < 0.05, corrected). These findings were replicated using an alternative protocol. Ventrolateral prefrontal cortex may be engaged in generating lies or withholding the truth.