1. Hepatocyte couplets can be routinely prepared from rat liver to pro
duce a suitable in vitro model for polarized primary cells. 2. Centrif
ugal elutriation provides a means of producing enriched subpopulations
of periportal and perivenous couplets from the same liver, thus provi
ding a means of studying the influence of zonal heterogeneity on hepat
obiliary function. 3. The maintenance of structural and secretory pola
rity demonstrated by hepatocyte couplets provides a convenient in vitr
o system for mechanistic studies of factors both regulatory and advers
ely affecting hepatobiliary functions. 4. Couplets are also uniquely a
ppropriate for specific studies of regulation at the biliary pole, on
the performance of junctions and on the maintenance and rate of transc
ytotic movement. 5. The possibility also exists that effects of an in
vivo pre-exposure to agents causing hepatobiliary dysfunction can be a
ssessed in couplets ex vivo.