Paraguay's 20-day preparations for their high-altitude clash were wasted as they went down 2-1 to Bolivia in La Paz, Chile ended Venezuela's romantic run with a 1-0 win and Peru condemned Uruguay to a second successive defeat at home.
Peru triumphed 3-1 at Montevideo's historic and once impregnable Centenario stadium where Venezuela had run out 3-0 winners in March.
The results left Chile and Paraguay with 10 points from six games, Venezuela with nine, Peru eight, Uruguay seven and Bolivia six.
Argentina, who lead the qualifying table with 11 points from five games, meet Brazil, who have nine, in Belo Horizonte on Wednesday while Ecuador and Colombia, both on four points, clash in Quito.
The top four teams qualify directly for the World Cup and the fifth plays off against the Oceania region winners.
Bolivia, whose chances depend heavily on winning matches in La Paz at 3,600 metres above sea level, gave veteran coach Ramiro Blacut a perfect start to his third stint in charge.
A diving header by Roger Suarez in the second half secured the points for Bolivia, who were reduced to 10 men when Juan Manuel Pena was sent off for violent conduct.
Luis Cristaldo, a survivor from the Bolivia team which played at the 1994 World Cup finals, opened the scoring early on before Jose Cardozo equalised for Paraguay before halftime.
The visitors had sent a group of players to Bolivia 20 days early to acclimatise while the top names, including Cardozo and Bayern Munich striker Roque Santa Cruz, who set up their goal, arrived this week.
FLAMBOYANT COACH
Venezuela, who had enjoyed an unprecedented run of wins, were brought down to earth on a wet night in San Cristobal.
They dominated the match, failed to break through Chile's defence and fell victim to a brilliantly-taken 84th minute goal by halftime substitute Mauricio Pinilla.
Uruguay's defeat against Venezuela cost flamboyant coach Juan Ramon Carrasco his job but debutant Jorge Fossati fared little better on Tuesday.
The hosts made a bright start but were knocked off course by Nolberto Solano's curling free kick for Peru in the 12th minute.
Claudio Pizarro scored on the break seven minutes later, then Uruguay had defender Gonzalo Sorondo sent off for hacking down, treading on and spitting at Roberto Palacios.
Peru repeatedly broke through the Uruguay defence but wasted their chances until Jefferson Farfan made it 3-0 in the second half. Diego Forlan headed the consolation goal for the sad Uruguayans.
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