The pathogenesis, diagnosis, and optimal therapy of gastroesophageal r
eflux disease continue to be intensely investigated. A focus is on hia
tus hernia as a contributor to sphincter incompetence and poor clearan
ce. Acid is the most important damaging constituent of gastric refluxa
te, but the importance of alkaline reflux and nonsteroidal drugs conti
nues to be debated. Exciting reports confirm that the human esophagus
secretes bicarbonate in significant quantity. Swallowed salivary bicar
bonate remains an important factor in the restoration of a neutral eso
phageal pH. Animal experiments confirm the presence of paracellular ba
rriers to diffusion, and intracellular mechanisms to buffer acid. Epid
ermal growth factors and their receptors are present in human esophage
al biopsies. The methodology and clinical usefulness of ambulatory pH
monitoring and manometry in adults and children continue to be debated
. The need for long-term treatment of reflux disease is underlined by
studies of natural history in adults, which indicate that symptoms rar
ely resolve spontaneously. Acid inhibition with omeprazole or high-dos
e H-2-receptor antagonists is the most effective medical therapy, and
appears to be safe during 5-year, continuous treatment. Nissen fundopl
ication had advantages over low-dose H-2-receptor antagonists in one 2
-year study, but the greater effectiveness of modern therapeutic regim
ens means that further comparisons are required. Economic modeling sho
ws that omeprazole is the most cost-effective medical treatment.