Background: Knowledge of the amount of gene order and synteny conservation between two species gives insights to the extent and mechanisms of divergence. The vertebrate Fugu rubripes (pufferfish) has a small genome with little repetitive sequence which makes it attractive as a model genome. Genome compaction and synteny conservation between human and Fugu were studied using data from public databases.Methods: Intron length and map positions of human and Fugu orthologues were compared to analyse relative genome compaction and synteny conservation respectivley. The divergence of these two genomes by genome rearrangement was simulated and the results were compared to the real data.Results: Analysis of 199 introns in 22 orthologous genes showed an eight-fold average size reduction in Fugu, consistent with the ratio of total genome sizes. There was no consistent pattern relating the size reduction in individual introns or genes to gene base composition in either species. For genes that are neighbours in Fugu (genes from the same cosmid or GenBank entry), 40–50% have conserved synteny with a human chromosome. This figure may be underestimated by as much as two-fold, due to problems caused by incomplete human genome sequence data and the existence of dispersed gene families. Some genes that are neighbours in Fugu have human orthologues that are several megabases and tens of genes apart. This is probably caused by small inversions or other intrachromosomal rearrangements.Conclusions: Comparison of observed data to computer simulations suggests that 4000–16 000 chromosomal rearrangements have occured since Fugu and human shared a common ancestor, implying a faster rate of rearrangement than seen in human/mouse comparisons.