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H.264/AVC adopts many directional spatial prediction models in block-based manner that neighboring pixels on the left and top sides yield prediction for the pixels in a data block to be encoded. However, such models may adapt poorly to the rich textures inside blocks of video signal. In this letter, a new lossless intra coding method based on pixel-wise interleave prediction is presented to enhance the compression performance of H.264/AVC. In our scheme, pixels are coded alternately with interleave prediction, which makes full use of reconstructed pixels to predict later ones in bidirectional or multidirectional manner. Extensive experiments demonstrate that compared to the H.264/AVC standard, our scheme has higher compression ratio, especially for sequences of high resolution. In addition, the scheme can be regarded as a frame-level coding mode and can be easily integrated into the H.264/AVC framework.