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Thyroid-status-dependent changes in lipid/phospholipid profiles in rat liver mitochondria were examined and attempts were made to correlate the observed changes with kinetic parameters of succinate-2,6-dichloroindophenol reductase (SDR) and membrane fluidity. Thyroidectomy caused substantial decrease in the total phospholipid and cholesterol contents; the proportion of all phospholipid components was also decreased significantly (50–100% decrease). The energy of activation, E1, for SDR decreased with a concomitant increase in the membrane fluidity. Treatment with physiologic doses or replacement doses of L-thyroxine resulted in partial restoration of lipid/phospholipid components. However, the SDR activity decreased with a simultaneous elevation in the phase-transition temperature and significant decreases in E1 and E2. Treatment with L-thyroxine restored membrane fluidity to almost euthyroid values. Regression analysis suggested a role for phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol microdomains in modulating the SDR activity. Membrane fluidity was strongly correlated with total phospholipid, cholesterol, diphosphatidylglycerol and phosphatidyl-inositol, and the ratio of cholesterol/total phospholipid (mol/mol). [ABSTRACT FROM AUTHOR]