Three hundred and eighty-nine follow-up ultrasound examinations of 117 plaques were performed in a prospective study of 60 patients (42 male, 18 female; mean age: 63.1 ± 9.3 years). Follow-ups ranged between 2 and 67 months (mean: 37.1 months). High resolution ultrasound B-mode imaging in combination with specially designed three-dimensional plaque contour and volume reconstruction analysis and with a multigate pulsed Doppler intra-arterial flow velocity examination were used for a detailed evaluation of plaque morphology and local hemodynamics. Follow-up studies at 3- to 6-month intervals showed progression in 99 (25%), regression in 28 (7%) and no change in 262 (68%) examinations. Regression was most frequent in flat homogeneous and ulcerated plaques, but progression occurred more often in soft heterogeneous and irregularly surfaced ones. Secondary slow-flow zones and turbulences were significantly associated with irregular plaque surfaces and ulceration. In contrast, no significant reduction of both platelet and endothelial eicosanoid metabolites thromboxane (TXB2), prostacyclin, β-thrombo-globulin and platelet factor 4 (PF4) was found at repair versus progressive phases although TXB2 and PF4 values tended to be lower in regressive development. Thus, irregularly surfaced heterogeneous plaques in the presence of secondary flow zones are parameters indicating plaque instability; whether plaque regression is associated with reduced levels of platelet-derived vasoactive proteins remains unsettled.