The complete chromosomal sequence for chromosome 1 from Leishmania major Friedlin predicts that this chromosome has 79 protein-coding genes. Surprisingly, the first 29 of these genes are encoded in tandem on one strand of DNA, and the remaining 50 genes are encoded in tandem on the other. No RNA polymerase promoters, centromeric sequences or origins of DNA replication have been identified in the DNA sequence. Statistical analyses of the nucleotide content reveal striking, non-random, sequence-biases that are correlated with genome organization. Analysis of coding regions suggests that novel transcription processes in Leishmania may be responsible for the nucleotide bias, which in turn affects gene organization in the chromosome. These results also suggest that the region between the two units of in-tandem genes is a candidate for an origin of DNA replication.