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Orthogonal frequency division multiplexing (OFDM) systems empowered by multiple-antenna technology, known as MIMO-OFDM, have gained wide applications in high-rate wireless data communications. We focus on optimal channel estimation of MIMO-OFDM systems in this paper. A new method for pilot-tone design is presented that differs from existing work not only in its unique capability of estimating fast time-varying and frequency-selective fading channels, but also in the simplicity of its least square (LS) algorithm, free of matrix inversion. It is shown that the proposed new pilot-tones are actually orthogonal codes in the space-frequency domain, which achieve optimal channel estimation in the sense of obtaining the minimum mean square error (MSE) of channel estimation and thus inherit the same computational advantages as in the previous works. The design of the space-frequency codes (SFC) for a MIMO-OFDM system with any number of transmit antennas is studied and its effectiveness is demonstrated by computer simulations of a 2×2 MIMO system.