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A new differential scheme for space-time block-coded transmission in a flat-fading multiuser environment is developed in this paper. This scheme performs joint space-time interference cancellation and decoding, thus realizing diversity and rate gains, without requiring channel knowledge or bandwidth expansion. Our focus is on the case of two users each equipped with two transmit antennas for simplicity. However, the development readily extends to more than two users, to more than two transmit antennas per user, and to frequency-selective channels using previously published techniques.