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BACKGROUND Despite the similar rate of HP infection, the rate of gastric cancer (GC) differs in different regions of the country. There are conflicting reports for using a panel of serologic tests such as pepsinogens I, II (PG I and PG II), and gastrin for population screening. We designed this study to assess healthy appearing adults in Shiraz, southern Iran in order to evaluate the correlation of these serological tests with demographics and lifestyle in a region with a low rate of gastric malignancy. METHODS In a population-based study, 846 out of 1978 subjects who were selected by cluster random sampling based on postal code division in Shiraz agreed to participate in the present study. A questionnaire that included age, gender, weight and height, lifestyle such as physical activity, smoking and the use of nonsteroidal anti inflammatory drugs (NSAIDs) was completed. A blood sample was taken after overnight fasting for measurements of PG I, PG II and Cag A status by enzyme-linked immunosorbant assay (ELISA). Gastrin level was measured by radioimmunoassay (RIA). RESULTS The study included 305 men and 541 women. Their mean age was 50.53+11.4 (range: 35-99 years). The level of PG I was significantly more in males than females (116.6±57.1 vs. 103.1±55.8, p < 0.001), lower in older age groups (p = 0.01), and rural compared with urban residents (110.3+55.7 vs. 100.2+58.1, p = 0.02). The serum level of PG II was less in obese subjects (p = 0.5). There was no significant correlation between PG I, PG II, smoking, NSAID use and activity. Gastrin level were not correlated with any of the demographic characteristics. The level of Cag A was significantly different between males and females (30.5±37 vs. 37.7±41.7, p < 0.001), more in older subjects (p = 0.007) and non smokers (p = 0.001). The serum levels of PG I and PG I/PG II ratio decreased significantly in subjects with positive Cag A serology (p < 0.05). The ratio of PG I/PG II was lower than 3 in 35 (4.1%) subjects. CONCLUSION In this area, the PG I/PG II ratio is less than 3 in 4% of subjects of which most are positive for Cag A serology and older than 50. We recommend comparison of these findings with high GC mortality regions. [ABSTRACT FROM AUTHOR]