We describe here the first general survey of the genomic content and the coding capacity of the 1.1 Mb genome of Rickettsia prowazekii based on an analysis of a total of 200 kb of unique sequence data collected in a random manner. Based on nucleotide distribution profiles, we estimate that the R. prowazekii genome may have a coding density of 60%-70% and that it may contain a total of circa 800 genes. Here, we have tentatively identified and classified 173 of these genes. Our analysis suggests that the R. prowazekii genome is a highly derived, reduced genome that has lost many genes involved in amino acid biosynthetic pathways and regulatory functions. Furthermore, the R. prowazekii genome seems to lack glycolytic genes, but it does contain genes encoding components of the tricarboxylic acid cycle as well as of the electron transport system. We have also encountered a family of homologous genes coding for ATP/ADP translocases, as observed in several mitochondrial genomes. We relate these findings to previous phylogenetic studies that suggest that Rickettsia and mitochondria share a common ancestor.