N6-Isopentenyladenosine (i6A), an adenosine and mevalonate derivative, inhibits, like adenosine, TSH-induced cAMP increase and its related events (I- uptake and DNA synthesis) in FRTL-5 cells. This inhibition is dose-dependent and is measurable at 10(-8) M. However, unlike adenosine, i6A prevents TSH-promoted microfilament disassembly. The effect of i6A on cytoskeletal structure is antagonized by pertussis toxin and could be assigned to its N6 substitution since it can be mimicked by other synthetic N6-adenosine derivatives. It is suggested that a step beyond cAMP is involved, since i6A prevents also microfilament disassembly induced by 8-bromo-cAMP. This is the first demonstration that an adenosine derivative, which is also an end-product of the isoprenoid pathway, affects cAMP-dependent microfilament organization.