This study emanates from the concern to evaluate human environmental disease from the point of view of physical environmental status and human activity profiles in spartial distribution contest in the city of Calabar, Cross River State Nigeria this research category is an ambit of descriptive epidemiology for the general survey of individual cases of etiology of diseases and then correlating them to their environmental characteristics/qualities. Calabar situates in the subtropical environment with hot solar radiation and correspondingly adequate supply of rainfall. Papodaski et al (1995) have categorized the city as belonging to a per humid ecological zone. Adequate supply of rainfall and high solar receipt, provide a suitable  breeding ground for a number disease vectors such as Mosquitoe, tsetse fly, felea, redfly (drosophila) and so on. Human land use occupation has equally contributed in shaping the environmental characteristics over the itinerant economic and geographic landscape. This mosaic of Human environmental images have a lot in store for explanation in environmental epidemiology. The study population is the entire adult residents in Calabar. The study is therefore challenged by the need to evaluate the true perspectives of the disease burden prevalent in the spatial environmental context. To effectively obtain field data information, the questionnaire instrument was administered to respondents to elicit information on their health history. Preceding this was delimitation of the entire city domain on the criteria of “Residents environmental Status” such as “flooded areas”, permanently waterlogged” slum/ghetto areas etc. Twelve of such categories were designated. Accordingly, a number diseases such as malaria, dysetry, schistrosominsis etc were selected for identification through interview. The data obtained from the field was presented as “Environmental disease matrix of Calabar”. The data was analyzed based on the technique of one-way analysis of variance. In line with decision rule, the rcal ratio is greater than the Fcritical value at Alpha level of 0.05. it was therefore evident that Ho was rejected, which the “Hi” was accepted indicating that there is significant variation in the disease burden prevalence rate over the city of Calabar.