Gastroretentive dosage forms have potential for use as controlled-release drug delivery systems. The use of floating dosage forms (FDFs) is one method to achieve prolonged gastric residence times (GRTs), providing opportunity for both local and systemic drug action. Multiple-unit systems avoid the 'all-or-nothing' gastric emptying nature of single-unit systems. A freeze-dried calcium alginate multiple-unit FDF has been developed which demonstrated favourable in vitro floating characteristics. The aim of this study was to investigate the in vivo behaviour of this system compared to a multiple-unit non-floating dosage form manufactured from identical material. The study was performed in seven healthy volunteers, who swallowed the radiolabelled formulations after a standard breakfast. Transit was monitored by gamma-scintigraphy and subjects were maintained in the fed state. Prolonged GRTs of over 5.5 h were achieved in all subjects for the floating formulations, which remained high up in the stomach for the whole of the test period. In contrast, the non-floating beads displayed short GRTs, with a mean onset emptying time of 1 h. The results of this study suggest that, in the fed state, this FDF has potential for sustained drug delivery for either local or systemic purposes.