Islet amyloid polypeptide is known to localize to the adult human Beta cell. We analysed the immunoreactivity for islet amyloid polypeptide in a series of 29 human fetal pancreata (9-24 weeks of gestation) with respect to age dependency and cellular localization using an antibody raised against synthetic rat islet amyloid polypeptide 12-37. Cells immunoreactive for islet amyloid polypeptide were demonstrated in low numbers from week 13 onwards while insulin positivity was already present at 9 weeks of gestation. In the age group 13-16 gestational weeks, cells positive for insulin were 20-fold more frequent than cells positive for islet amyloid polypeptide. This difference gradually disappeared with age, reaching parity in the adult gland. Double immunostaining demonstrated that all islet amyloid polypeptide immunoreactivity co-localized with insulin. Co-expression of insulin and islet amyloid polypeptide was more frequent in Beta-cell clusters (greater than or equal to 10 cells) than in single Beta cells; islet amyloid polypeptide positivity was present in 58 +/- 9% (mean +/- SEM; n = 4) of fetal, 88 +/- 9% (n = 3) of neonatal and 100% (n = 3) of adult clustered Beta cells, and only 8-18% of the single Beta cells. The results suggest that the developing fetal Beta cells, dependent on age and localization, differ in their capacity to express detectable amounts of immunoreactive islet amyloid polypeptide. Beta-cell maturation might therefore be associated with islet amyloid polypeptide expression.